Vaginal rings are torous shaped devices designed to deliver a relatively constant dose of drug to the vagina usually over a period of weeks to months. Typically, they are made of a silicone elastomer and contain a drug released by diffusion though the elastomer. The most common commercial applications have been to deliver low doses of steroids for post-menopausal vaginal conditions. They have also been under development for use in contraception and hormone replacement therapy. Vaginal rings have also been used to administer spermicides, as well as a variety of locally or systematically active medicaments. Vaginal rings have provided several advantages in that their use is controlled by the female; they allow for a better regulated dose of drug without attention by the user; and they avoid the destruction (by the intestine and by first pass through the liver) of an appreciable portion of the daily dosage of some steroids compared to their orally delivered counterparts.
The use of a vaginal ring to deliver drugs requires a ring design that regulates the release rate so as to provide the user with the appropriate daily dose. Among the important factors governing release are the solubility of the drug in the ring elastomer, the surface area of the drug reservoir, the distance the drug must diffuse through the ring body to reach its surface and the molecular weight of the drug. If very high release rates are desired, they can be attained by a drug load at the ring surface as is characteristic of the homogeneous matrix ring design. This design, however, suffers from rapidly declining release rates as the distance the drug must travel to reach the ring surface increases as the drug load near the surface is depleted. If moderately high release rates are needed to provide the appropriate dose, a design which modulates release rate by imposing a layer of drug-free elastomer between the drug reservoir and the ring exterior is appropriate. This may be attained by coating a homogeneous ring, or to conserve drug, by incorporating a drug-free core, a shell design may be used. If an even lower release rate is desired, the drug may be confined to a small diameter at the center of the ring ("core ring"). Finally, the drug-loaded core may not encircle the ring but instead be of short length. Numerous types of vaginal rings have been described in the patent and non-patent literature alike. See, e.g., U.S. Pat. Nos. 4,012,496 and 4,155,991 (both to Schopflin et al.), 4,292,965 (Nash), 3,545,439 (Duncan), 3,920,805 (Roseman), 3,991,760 and 3,995,634 (both to Drobish et al.), 3,995,633 (Gougen), 4,250,611 and 4,286,587 (both to Wong), 4,596,576 (de Nijs); W095/00199 (Lehtinen et al.), NL 8500-470-A; and Apter et al., Contraception 42:285-295 (1990), Burton et al., Contraception 17:221-230 (1978), Burton et al., contraception 19:507-516 (1979), Jackanicz, Contraception 24:323-339 (1981), Sivin et al., Contraception 24:341-358 (1981), Timmer et al., Contraception 43:629-642 (1990), and Toivonen, Contraception 20:511-518 (1979).
Vaginal rings have been used experimentally to deliver the contraceptive agent, ethynylestradiol. However, an undesirable percentage of women who have used vaginal rings for this purpose had complained of nausea and vomiting, particularly from the first cycle of use of the rings due to an initial burst of steroid release. The manufacture of the so-called "core" rings presents additional problems. One problem is the physical one of placing the cores in the ring body by techniques adapted to facile manufacture. Another is that drugs with reactive groups such as ethynyl, amino groups, or sulfhydryl groups may prevent vulcanization of preferred silicone polymers. One method of introducing short lengths of drug-loaded cores is to mold a half ring with a center groove, place the core in the groove, change molds and inject the second half of the ring. This technique, while feasible, requires two molding steps for manufacture of the ring body. It also limits elastomer choice when dealing with reactive drugs such as ethynylestradiol.
Hence, a need remains for a vaginal ring that does not cause nausea and vomiting, and other problems associated with some devices, while still providing the other advantages that vaginal rings have offered.